Establishment And Mechanistic Study Of Formaldehyde-induced Asthma Rat Model

With the development of modern society,indoor decoration is becoming popular, making the indoor air pollution issue increasingly serious.Formaldehyde(FA)is one of the most important indoor air pollutants during such decoration,which owns characteristics of long-term pollution,wide-range sources and high toxicity.The immune toxicity of this chemical is mainly manifested by the increased sensitivity of the immune response,causing allergic rhinitis and asthma.Among those effects induced by FA,FAinduced asthma is highly risky for human and even lethal in seriously situation.For the mechanism of this respiratory disease,the traditional theories considered FA as a kind of allergen which may cause asthma via the specific IgE pathway.However,numerous epidemiological studies showed the undetectable FA-specific IgE in bodies of patients suffered from FA-induced asthma,suggesting that FA may induce asthma via other pathways.In 2007,Mendell reviewed two possible pathways of FA-induced asthma:If FA couldⅰ)cause bronchial inflammation by itself orⅱ)act as an adjuvant for inducing allergy to common allergens.On one side,it was demonstrated that pre-exposure to FA can induce transient airway hyperresponsiveness(AHR)in FA-exposed persons and animals.On the other side,FA also displays adjuvant role on the sensitization to common allergens in animal,as well as exacerbates allergen-induced asthma syndromes in the controlled human exposure experiments from one epidemiological study.Nevertheless, in most cases,these two potential effects of FA are difficult to distinguish.In order to establish the FA-induced asthma occupational asthma model and distinguish the two possible roles of FA,we carried out the present mechanistic investigation FA-induced asthma in rat model.The experimental results are as below:1.The establishment of FA-induced asthma rat modelIn the present study,40 Wistar rats in five experimental groups are exposed to:ⅰ) saline;ⅱ)ovalbumin(OVA);ⅲ)OVA + FA 0.5 mg/m~3;ⅳ)OVA + FA 3.0 mg/m~3 and v) FA 3.0 mg/m~3.0.5 mg/m~3 and 3.0 mg/m~3(the current and previous occupational exposure limit in China)of gaseous FA are administrated to the animals for 6 h/d before and during the process of OVA immunization or saline treatment.The outcomes are in situ lung function analysis,cytokine measurement and histological observation in the lungs of FA-induced asthma rats.After challenge of 1%OVA aerosol for 7 days,series of testing was done,including AHR testing,lung section Hematoxylin and eosin(H&E)staining, cell counting in bronchoalveolar lavage fluid(BALF)and enzyme-linked immuno sorbent assay(ELISA)for pulmonary interleukin-4(IL-4)/interferon-γ(IFN-γ).Results from MCH testing and H&E staining showed that the experimental rats with both FA exposure only and FA + OVA combined exposure exhibited several types of asthma syndromes such as AHR,suggesting that FA-induced asthma rat model has been successfully established,which offer us both models investigating FA direct and indirect exposure on asthma.This model is expected to be applied in the systematic mechanic studies of FA-induced asthma.2.Elucidation of the direct and indirect effects of FA on asthmaBy using the differentiated model for either the direct or indirect effects of FA on asthma,the present study made a preliminary view on the possible mechanisms of FAinduced asthma.The results showed that the airway response,airway structure change, cells counting in BALF and pulmonary IL-4 level were elevated significantly in 0.5 and 3.0 mg/m~3 FA exposured OVA-immunized rats,suggesting that FA may facilitate or aggravate OVA-induced asthma by increasing EOS inflammation and stimulating Th-2 type inflammatory reaction.For the 3.0 mg/m~3 FA alone group,on one side,the lasting AHR as well as significantly enhanced the pulmonary IFN-γlevel were observed in this group;on the other side,there is no significantly difference in the airway structure and EOS counting of this group comparing with the negative control.Interestingly,the EOS ratio and pulmonary IL-4 expression was significantly depressed,indicating that high level of FA exposure alone may induce asthma syndromes like AHR via the stimulation of Th-1 type of immunology response and probably non-EOS inflammation.